Nephron最新文献

Background: Sex differences exist in kidney physiology and disease which are underpinned by the biological actions of the sex hormones estrogen, progesterone and testosterone. In this review, we present an up-to-date discussion of the hormonal and molecular signalling pathways implicated in sex differences in kidney health and disease.

Summary: Estrogen and progesterone have protective effects on renal blood flow, glomerular filtration rate and nephron ion and water reabsorptive processes, whereas testosterone tends to compromise these functions. The biological effects of estrogen appear to be the most important in reinforcing kidney function and protecting against kidney diseases in females. The actions of estrogen are myriad but all tend to bolster kidney physiology to maintain a steady-state and adaptable extracellular fluid volume (ECFV) and blood pressure. Estrogen safeguards ECFV homeostasis by stimulating renal epithelial sodium channel (ENaC) and water channel (AQP2) expression and transport function. Renal maintenance of ECFV within narrow physiological limits is a first-line of defense against hypertension and lowers the risk of cardiovascular disease in women. The estrogenic and XX chromosome basis for a female advantage are evident in a wide range of kidney diseases including acute kidney injury, chronic kidney disease, end-stage kidney disease, diabetic kidney disease, and polycystic kidney disease. The molecular mechanisms involve estrogen regulation of nephron ion and water transport, genetic immunogenic responses, activation of the protective arm of the renin angiotensin-aldosterone system and XX chromosome reinforcement of immune responses. Kidney disease can also predispose patients to cancer and women are protected in renal cancer with lower incidence, morbidity, and mortality than age-matched men with the disease.

Key messages: This review underscores the importance of incorporating sex-specific considerations into clinical practice and basic research to bridge the gap in understanding and addressing biological sex disparities in kidney disease and renal cancer.

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Introduction: Middle-aged and older individuals often face significant challenges in adopting digital health solutions, leading to a digital divide that hinders their ability to benefit from mobile health (mHealth) interventions. This study aims to investigate the specific requirements of middle-aged and older patients with chronic kidney disease (CKD) for self-management through mobile health applications (mHealth apps), using the Kano model.

Methods: A multicenter cross-sectional survey was conducted from April to September 2023 in five hospitals across Sichuan, Shandong, Guangdong, and Shaanxi provinces in China. The Kano model was employed to analyze participants' preferences regarding mHealth apps for self-management.

Results: Out of 359 participants (57.1% men, predominantly aged 45-54), the study identified essential and desirable features for mHealth apps. Essential attributes include comprehensive CKD information and robust privacy protection. Key to enhancing user satisfaction are features like symptom and medication management, access to medical insurance information, and app interface simplicity. Additional attractive features for increasing app appeal include diet management, exercise guidance, and customizable text size.

Conclusion: This study identifies critical mHealth app features for self-management in middle-aged and older CKD patients, emphasizing the importance of user-centric design. The findings provide valuable insights for app developers to create tailored solutions that cater to the specific needs of this demographic, potentially enhancing their self-management capabilities.

Introduction: Sepsis is the leading contributor to acute kidney injury (AKI), responsible for 45% to 70% of AKI occurrences. Despite this, septic AKI is a highly multifactorial and complex condition, and our grasp of its pathogenesis is still not fully developed. Consequently, there remains a significant gap in effective diagnostic and therapeutic strategies for septic AKI.

Methods: In the in vitro experiments, BUMPT cells were exposed to lipopolysaccharides (LPS). In vivo experiments involved inducing sepsis in mice through administration of LPS injections. Additionally, in certain experiments, either a miR-455-5p mimic or an anti-miR-455-5p LAN was administered to the mice via injections into the tail vein. The mice were then sacrificed 24 hours following LPS administration for subsequent analysis.

Results: We observed a significant elevation in miR-455-5p levels within renal tubular cells following LPS-induced septic AKI. Our investigation revealed that NF-κB plays a crucial role in the upregulation of miR-455-5p. Inhibition of NF-κB using TPCA-1 prevented the rise in miR-455-5p levels in BUMPT cells (mouse proximal tubular cells from Boston University) cultured in vitro. ChIP assays confirmed that NF-κB directly interacts with the promoter region of the miR-455-5p gene in response to LPS treatment. Functionally, introducing miR-455-5p mimics intensified cell apoptosis, kidney damage, and the production of inflammatory cytokines, while silencing miR-455-5p had protective effects in septic mice. Notably, administering anti-miR-455-5p enhanced SOCS3 expression, whereas miR-455-5p mimics reduced SOCS3 levels following LPS exposure. Furthermore, our luciferase reporter assays demonstrated that SOCS3 is a direct target of miR-455-5p.

Conclusion: This study indicates a NF-κB/miR-455-5p/SOCS3 axis which can exacerbate kidney damage by enhancing renal inflammation. This process highlights potential therapeutic targets for managing septic AKI.

Introduction: Serious outbreaks related to Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) have been reported globally. In 2011, Germany experienced a significant outbreak of HUS caused by enteroaggregative Escherichia coli (EAEC) O104:H4 strain. Since then, no other outbreaks of this strain have been reported. This study aims to evaluate pediatric patients affected by the second documented worldwide outbreak of STEC-HUS (EAEC O104:H4 serotype) contaminating local drinking water.

Methods: Medical records of patients hospitalized in five pediatric intensive care units (PICU) diagnosed with STEC-HUS between July and September 2022 were evaluated retrospectively.

Results: Eighteen patients (14 girls, and 4 boys) were enrolled in the study. The median age was 7.4 [Intetquartile range (IQ) 1.3-17] years. Abdominal pain was the most common symptom (100%). The mean duration between symptom onset and development of STEC-HUS was 3 days (IQ 1-9). EAEC O104:H4 serotype was detected in the stool samples of eight patients. Neurological involvement was observed in three patients, cardiac involvement in two patients, and both in one patient. Two patients required respiratory support and dialysis was performed in 16 (88.8%) patients. Plasmapheresis was administered to two patients, and eculizumab was given to four. No mortality was reported during follow-up; the mean durations of PICU and hospital stays were 11.3 and 31.6 days, respectively.

Conclusion: Outbreaks of HUS can have severe implications on mortality and morbidity. However, timely diagnosis and implementation of appropriate supportive care, including dialysis, respiratory support, and suitable medical treatment for eligible patients, can lead to favorable outcomes.

Introduction: Acute kidney injury is associated with adverse outcomes, including death and dialysis. The goal of this study was to identify prognostic biomarkers of Acute Kidney Injury (AKI) that could be used across multiple phenotypes of AKI, and across different species.

Methods: Liquid chromatography/tandem mass spectrometry analysis of urine samples from three species (human, rat, mouse) and four etiologies of acute kidney injury identified five potential biomarkers; of which two were validated, complement C3 and vitamin D binding protein, in a cohort of 157 patients that developed AKI following cardiothoracic surgery. We studied the relationship between the biomarker's concentration in the urine and the development of a composite primary endpoint (stage 3 acute kidney injury within 10 days or death within 30 days).

Results: Of the153 patients who developed acute kidney injury following cardiovascular surgery; 17 met the combined primary outcome. The median concentration of urine complement C3 adjusted to urine creatinine had the best predictive value and was significantly higher in the primary-outcome group than in the controls. Similarly, the median concentration of vitamin D binding protein was higher in the primary-outcome group.

Conclusions: The studies provide proof in principle that cross-species discovery analyses could be a valuable tool for identifying novel prognostic biomarkers in AKI. Urine complement C3 and vitamin D binding protein could be promising early predictors of adverse outcome in patients who develop AKI after cardiac surgery.

Introduction: Recommendations to move to a race free estimating equation for glomerular filtration rate have gained increasing prominence since 2021. We wished to determine the impact of any future adoption upon the CKD patient population of a large teaching hospital, with a population breakdown largely similar to that of England as a whole.

Methods: We compared four estimating equations (MDRD, CKD-EPI (2009), CKD-EPI (2021) and EKFC) using the Bland-Altman method. Bias and precision were calculated (in both figures and percentages) for all patients with CKD and specific subgroups determined by age, ethnic group, CKD stage and sex. CKD stage was assessed using all four equations.

Results: All equations studied had a positive bias in South Asian patients and a negative bias in Black patients compared to CKD-EPI (2021). Similarly, there was a positive bias in White patients across all equations studied. Comparing CKD-EPI (2009) and EKFC this positive bias increased as patients aged, the opposite was seen with MDRD. Between 10% and 28% of patients in our dataset changed their CKD staging depending upon estimating equation used.

Discussion: Our work confirms previous findings that the MDRD equation overestimates eGFR in South Asians and underestimates eGFR in Blacks. The alternative equations also demonstrated similar bias. This may, in part, explain the health inequalities seen in ethnic minority patients in the UK. Applying our findings to the UK CKD population as a whole would result in anywhere from 260,000 - 730,000 patients having their CKD stage reclassified, which in turn will impact secondary care services.

Background: Hypertension (HTN) is a common side effect of tacrolimus (Tac), the first-line antirejection medication for kidney transplant recipients. The impact of immediate-release tacrolimus (Tac IR) dosed twice daily versus extended-release tacrolimus (Tac ER) dosed once daily on long-term blood pressure control in kidney transplant recipients remains understudied. This study aims to compare the use of Tac IR versus Tac ER in kidney transplant recipients and evaluate the effects of the different formulations on systolic blood pressure (SBP), diastolic blood pressure (DBP), and HTN crisis.

Methods: This retrospective cohort study at a single institution collected baseline characteristics, time-varying exposure to Tac IR versus Tac ER, SBP, DBP, HTN crisis, and confounders at each posttransplant visit. A marginal structural linear mixed-effects model was employed to analyze the longitudinal blood pressure control in kidney transplant recipients receiving Tac IR and Tac ER.

Results: The final analysis included 654 patients, with mean ages of 52.0 years for Tac IR and 50.3 years for Tac ER. Males constituted 56.7% in Tac IR and 55.0% in Tac ER. Notably, the black population had 2.44 times higher odds of receiving Tac ER after adjusting for the rest of the baseline characteristics. No difference was found between longitudinal SBP (p = 0.386, 95% CI: -1.00, 2.57) or DBP (p = 0.797, 95% CI: -1.38, 1.06).

Conclusion: Our study indicates that posttransplant patients taking Tac ER exhibit no difference in chronic SBP and DBP controls compared to Tac IR.

Introduction: Lysinuric Protein Intolerance (LPI) is a multisystemic inborn error of metabolism with a variable clinical expressivity, that usually begins in childhood with growth failure and gastroenterological/neurological problems related to the altered urea cycle and later complications involving the renal, pulmonary and immuno-hematological systems.

Case report: We present the case of a 40-year-old woman suffering from chronic kidney disease in the context of a LPI, whose diagnosis was challenging because the signs of the disease were always blurred and the patient never manifested critical episodes typical of this multisystemic disease. In addition to renal disease, splenomegaly, thrombocytopenia, elevated lactate dehydrogenase (LDH), hyperferritinemia and hypertriglyceridemia were also present. A thorough investigation of the patient's food preferences revealed her spontaneous aversion to protein-containing foods and excessive drowsiness during the occurrence of infectious episodes or on the rare occasions of excessive protein intake, although without ever coming to medical attention. These nuanced signs led us to suspect an impairment of the urea cycle and ultimately allowed us to narrow down the diagnosis to LPI through biochemical and genetic investigations.

Conclusion: Nephrologists should consider LPI in the differential diagnosis, whenever a patient presents with mixed proteinuria, tubular dysfunction and/or chronic kidney failure of unknown origin. In these circumstances, we suggest looking for other signs such as growth failure, signs and symptoms ascribed to urea-cycle impairment, pulmonary involvement, hepatosplenomegaly and laboratory alterations such as pancytopenia, hyperferritinemia, lipid abnormalities, elevated LDH.